Food allergy is a growing and serious health concern in the United States. There is no definitive treatment for PN or other food allergies. In our initial R01 grant project, we developed Food Allergy Herbal Formula-2 (FAHF-2) and showed that it completely blocked PN-induced anaphylaxis in a murine model and had a high safety profile. Protection persisted up to 6 months post therapy, and was associated with immunomodulatory effect, but not overall immune suppression. These results demonstrate that FAHF-2 is an optimal candidate for developing a botanical drug for treating food allergies. We began the FAHF-2 phase I clinical study have obtained FDA IND and IRB approvals. In this renewal application, we propose to investigate the persistent effect of FAHF-2 on food allergy, and investigate the immunotherapeutic mechanisms, and chemical and pharmacological characteristics of FAHF-2. We will pursue two specific Aims to continue this study. Aim #1. Investigate the safety and efficacy of FAHF-2 in food allergy patients: In this aim we will investigate the safety and efficacy of FAHF-2 on PN, TN, fish, and shellfish allergies, the most severe and chronic food allergies, in a12-45 year old age group. We are conducting an acute phase I study, followed by a long-term, open-label extension study of 6 months duration. After completing these safety studies, we will conduct a phase II double-blind, randomized, placebo-controlled trial. We will use standard methods such as double- blind, placebo-controlled oral food challenges to evaluate the clinical outcomes including long-term efficacy. We will also study the immunomodulatory mechanism focusing on IFN-3 production of CD8+ T cells. Aim #2. Refine FAHF-2 product and Investigate chemical and pharmacological characteristics of B-FAHF-2: Our current IND, FAHF-2, is a partially refined, but still curded herbal product. We propose to further refine this product, using butanol purification because butanol fractionation (B-FAHF-2) significantly reduced the effective daily dose and remained efficacy in our animal model of PNA. B-FAHF-2 might be the preferred starting point for isolation of active components. We will use a combination of chemical analysis (HPLC, mass spectrometry and NMR) and bioassays to isolate and identify active components in B-FAHF-2, and then begin preliminary pharmacokinetic studies in mice. This is the first clinical investigation of a botanical drug for multiple persistent food allergies. Accomplishing this study will be of fundamental importance to validate the possible clinical usefulness of this Chinese herbal medicine in PNA and other food allergies, and to understand the mechanisms of action. We will also be able to further refine FAHF-2 product to improve our clinical study, and identify active compounds for the purpose of understanding pharmacological characteristics of this complex botanical product Ultimately, this study may lead to a safe and effective herbal therapy for food allergy. PUBLIC HEALTH RELEVANCE: Food allergy is a growing and serious health concern in the US and is now the leading cause of anaphylactic reactions;at present, there is no definitive treatment for peanut or other food allergies. During our initial R01 grant project, we generated Food Allergy Herbal Formula (FAHF-2) derived from a classical traditional Chinese medicine formula, and demonstrated its efficacy, safety and persistent effect in a murine model of peanut allergy;we propose in this renewal to investigate the safety, efficacy and systemic immunotherapeutic mechanisms of FAHF-2 on peanut, treenut, fish and shellfish allergies of patients ages 12-45, for which we have received IND approval under the botanical drug program (IND77,468). This will foster the development of scientific knowledge of TCM treatment for improving the health, productivity, independence, and quality of life of persons with food allergies and is thus congruent with the goals of Healthy People 2010 and may lead to a safe and effective herbal therapy for food allergy.